Abstract
Filamentous fungi harbor a vast potential for secondary metabolite (SM) biosynthesis, yet the biological functions of numerous biosynthetic gene clusters (BGCs) remain obscure. In Fusarium graminearum, a devastating cereal pathogen, SMs are best known as virulence factors, but their broader contributions to fungal physiology are poorly defined. Here, we present a genome-scale functional dissection of 53 predicted SM-BGCs by constructing a knockout library targeting cluster backbone genes and systematically quantifying 24 phenotypic traits, generating 1,272 phenotypic measurements. This dataset reveals that secondary metabolism is not a dispensable metabolic burden; instead, SM-BGCs are broadly integrated into vegetative growth, asexual development, and abiotic stress adaptation. Transcriptome analyses further uncover pronounced spatiotemporal regulation and tissue-dependent requirements of SM-BGCs during infection of wheat heads versus coleoptiles, thereby revealing an ecological dimension of pathogenesis. Mechanistic investigation identified two previously uncharacterized clusters, PKS-type BGC36 and NRPS-type BGC47, as critical for full virulence. BGC36 positively regulates deoxynivalenol (DON) biosynthesis, whereas disruption of BGC47 compromises cell wall/membrane stress tolerance and is associated with reduced phosphorylation of the kinase Mgv1, impaired DON-toxisome formation, and reduced DON production. Together, our findings establish fungal secondary metabolism as a core physiological buffer against environmental fluctuations that supports homeostasis and virulence, and they provide a comprehensive genetic resource for dissecting the chemical biology of Fusarium.
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Claims 6
Claim · model-written summary
Fusarium secondary metabolite gene clusters contribute broadly to growth, asexual development and abiotic stress adaptation.
- Taxon
- Fusarium graminearum
Fusarium graminearumt0 - Gene
- SM-BGCse0
- Outcome
- vegetative growth, asexual development, and abiotic stress adaptatione0
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
_on_Corn_(Zea_mays)_at_Waimea%2C_Hawaii.jpg?width=500)
Verbatim
e0“SM-BGCs are broadly integrated into vegetative growth, asexual development, and abiotic stress adaptation”
t0“Fusarium graminearum”
Claim · model-written summary
SM-BGCs have spatially and temporally regulated requirements during infection of wheat heads versus coleoptiles.
- Taxon
- Fusarium graminearum
Fusarium graminearumt0 - Organ / stage
- wheat heads versus coleoptilese0
- Interactor
- wheat
Triticum aestivume0host - Gene
- SM-BGCse0
- Outcome
- spatiotemporal regulation and tissue-dependent requirementse0
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
_on_Corn_(Zea_mays)_at_Waimea%2C_Hawaii.jpg?width=500)

Verbatim
e0“spatiotemporal regulation and tissue-dependent requirements of SM-BGCs during infection of wheat heads versus coleoptiles”
t0“Fusarium graminearum”
Claim · model-written summary
BGC36 is critical for full virulence.
- Taxon
- Fusarium graminearum
Fusarium graminearumt0 - Interactor
- wheat
Triticum aestivume1 - Gene
- BGC36e0
- Outcome
- full virulencee0
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
_on_Corn_(Zea_mays)_at_Waimea%2C_Hawaii.jpg?width=500)

Verbatim
e0“PKS-type BGC36 and NRPS-type BGC47, as critical for full virulence”
e1“spatiotemporal regulation and tissue-dependent requirements of SM-BGCs during infection of wheat heads versus coleoptiles”
t0“Fusarium graminearum”
Claim · model-written summary
BGC47 is critical for full virulence.
- Taxon
- Fusarium graminearum
Fusarium graminearumt0 - Gene
- BGC47e0
- Outcome
- full virulencee0
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
_on_Corn_(Zea_mays)_at_Waimea%2C_Hawaii.jpg?width=500)
Verbatim
e0“PKS-type BGC36 and NRPS-type BGC47, as critical for full virulence”
t0“Fusarium graminearum”
Claim · model-written summary
BGC36 positively regulates deoxynivalenol biosynthesis.
- Taxon
- Fusarium graminearum
Fusarium graminearumt0 - Gene
- BGC36e0
- Outcome
- deoxynivalenol (DON) biosynthesise0
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
_on_Corn_(Zea_mays)_at_Waimea%2C_Hawaii.jpg?width=500)
Verbatim
e0“BGC36 positively regulates deoxynivalenol (DON) biosynthesis”
t0“Fusarium graminearum”
Claim · model-written summary
BGC47 disruption compromises cell wall and membrane stress tolerance and is associated with reduced Mgv1 phosphorylation, DON-toxisome formation and DON production.
- Taxon
- Fusarium graminearum
Fusarium graminearumt0 - Treatment
- disruption of BGC47e0
- Gene
- BGC47e0
- Outcome
- cell wall/membrane stress tolerancee0
- Direction
- compromisese0
Not reportedComparator
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
_on_Corn_(Zea_mays)_at_Waimea%2C_Hawaii.jpg?width=500)
Verbatim
e0“disruption of BGC47 compromises cell wall/membrane stress tolerance and is associated with reduced phosphorylation of the kinase Mgv1, impaired DON-toxisome formation, and reduced DON production”
t0“Fusarium graminearum”